No relevant pharmacokinetic drug-drug interaction between nintedanib and pirfenidone

Eur Respir J. 2019 Jan 10;53(1):1801060. doi: 10.1183/13993003.01060-2018. Print 2019 Jan.

Abstract

Nintedanib and pirfenidone are approved treatments for idiopathic pulmonary fibrosis (IPF). This open-label, two-group trial investigated the pharmacokinetic drug-drug interaction between these two drugs in patients with IPF.Subjects not treated with antifibrotics at screening (group 1, n=20) received a single nintedanib dose (150 mg) followed by pirfenidone (titrated to 801 mg thrice daily) for 3 weeks, with a further single nintedanib dose (150 mg) on the last day (day 23). Subjects treated with pirfenidone at screening (group 2, n=17) continued to receive pirfenidone alone (801 mg thrice daily) for 7 days, then co-administered with nintedanib (150 mg twice daily) for a further 7 days, before single doses of both treatments on day 16.In group 1, adjusted geometric mean (gMean) ratios (with/without pirfenidone) were 88.6% and 80.6% for nintedanib area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. In group 2, gMean ratios (with/without nintedanib) were 97.2% and 99.5% for pirfenidone AUC and Cmax, respectively. For all parameters, the 90% confidence intervals included 100%, suggesting similar exposure for administration alone and when co-administered. Both treatments were well tolerated.These data indicate there is no relevant pharmacokinetic drug-drug interaction between nintedanib and pirfenidone when co-administered in IPF patients.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Drug Administration Schedule
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Indoles / administration & dosage*
  • Indoles / pharmacokinetics
  • Male
  • Middle Aged
  • Patient Safety
  • Pyridones / administration & dosage*
  • Pyridones / pharmacokinetics
  • Severity of Illness Index
  • Treatment Outcome
  • United Kingdom

Substances

  • Indoles
  • Pyridones
  • pirfenidone
  • nintedanib